Document Detail


Additive effects characterize the interaction of antibodies involved in neutralization of the primary dualtropic human immunodeficiency virus type 1 isolate 89.6.
MedLine Citation:
PMID:  11533181     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Human immunodeficiency virus-type I (HIV-1) infection elicits antibodies (Abs) directed against several regions of the gp120 and gp41 envelope glycoproteins. Many of these Abs are able to neutralize T-cell-line-adapted strains (TCLA) of HIV-1, but only a few effectively neutralize primary HIV-1 isolates. The nature of HIV-1 neutralization has been carefully studied using human monoclonal Abs (MAbs), and the ability of such MAbs to act in synergy to neutralize HIV-1 has also been extensively studied. However, most synergy studies have been conducted using TCLA strains. To determine the nature of Ab interaction in HIV-1 primary isolate neutralization, a panel of 12 anti-HIV-1 human immunoglobulin G (IgG) MAbs, specific for epitopes in gp120 and gp41, were used. Initial tests showed that six of these MAbs, as well as sCD4, used individually, were able to neutralize the dualtropic primary isolate HIV-1(89.6); MAbs giving significant neutralization at 2 to 10 microg/ml included 2F5 (anti-gp41), 50-69 (anti-gp41), IgG1b12 (anti-gp120(CD4bd)), 447-52D (anti-gp120(V3)), 2G12 (anti-gp120), and 670-D (anti-gp120(C5)). For studies of reagent interaction, 16 binary combinations of reagents were tested for their ability to neutralize HIV-1(89.6). Reagent combinations tested included one neutralizing MAb with sCD4, six pairs consisting of two neutralizing MAbs, and nine pairs consisting of one neutralizing MAb with another non-neutralizing MAb. To assess the interaction of the latter type of combination, a new mathematical treatment of reagent interaction was developed since previously used methods could be used only when both reagents neutralize. Synergy was noted between sCD4 and a neutralizing anti-gp120(V3) MAb. Antagonism was noted between two pairs of anti-gp41 MAbs (one neutralizing and one non-neutralizing). All of the other 13 pairs of MAbs tested displayed only additive effects. These studies suggest that Abs rarely act in synergy to neutralize primary isolate HIV-1(89.6); many anti-HIV-1 Abs act additively to mediate this biological function.
Authors:
F Verrier; A Nádas; M K Gorny; S Zolla-Pazner
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of virology     Volume:  75     ISSN:  0022-538X     ISO Abbreviation:  J. Virol.     Publication Date:  2001 Oct 
Date Detail:
Created Date:  2001-09-04     Completed Date:  2001-10-11     Revised Date:  2013-04-18    
Medline Journal Info:
Nlm Unique ID:  0113724     Medline TA:  J Virol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  9177-86     Citation Subset:  IM    
Affiliation:
Department of Pathology, New York University School of Medicine, New York, New York 10016, USA.
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MeSH Terms
Descriptor/Qualifier:
Antibody Specificity*
Cell Line
HIV Antibodies / immunology*
HIV Infections / immunology,  virology*
HIV-1 / immunology*
Humans
Grant Support
ID/Acronym/Agency:
AI 27742/AI/NIAID NIH HHS; AI 32424/AI/NIAID NIH HHS; AI 36085/AI/NIAID NIH HHS; HL 59725/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/HIV Antibodies
Comments/Corrections
Comment In:
J Virol. 2002 Oct;76(20):10577; author reply 10578   [PMID:  12239339 ]

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